A Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 247
- 试验地点
- 46
- 主要终点
- Number of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The main purpose of this study is to evaluate the long-term safety of PTC923 in participants with phenylketonuria, and to evaluate the changes from baseline in dietary phenylalanine (Phe)/protein consumption.
详细描述
Eligible participants are:
Feeder participants: those who have completed a Phase 3 PTC Therapeutics (PTC) sponsored feeder study.
Non-feeder controlled participants: those who have not completed a feeder study and have blood Phe levels <360 μmol/L at study entry.
Non-feeder uncontrolled participants: those who have not completed a feeder study and have blood Phe levels ≥360 μmol/L at study entry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medical history of at least 2 blood Phe measurements ≥600 μmol/L.
- •Women of childbearing potential must have a negative pregnancy test at screening and agree to abstinence or the use of at least one highly effective form of contraception for the duration of the study, and for up to 90 days after the last dose of the study drug.
- •Males who are sexually active with women of childbearing potential who have not had a vasectomy must agree to use a barrier method of birth control during the study and for up to 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period.
- •Willing to continue current diet unchanged while participating in the study (unless specifically instructed to change diet during the study by the investigator).
排除标准
- •Inability to tolerate oral medication.
- •A female who is pregnant or breastfeeding, or considering pregnancy.
- •Serious neuropsychiatric illness (for example, major depression) not currently under medical control, that in the opinion of the investigator or PTC, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant.
- •Past medical history and/or evidence of renal impairment and/or condition including moderate/severe renal insufficiency (glomerular filtration rate [GFR] <60 milliliters [mL]/minute [min] min as estimated most recently during qualifying participation in a feeder study) and/or under care of a nephrologist.
- •Any other condition that in the opinion of the investigator or PTC, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant.
- •Requirement for concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate).
- •Concomitant treatment with tetrahydrobiopterin (BH4) supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).
- •Additional criteria for non-feeder participants who did not participate in a feeder study:
- •Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, and peptic ulcer disease, etc) that could affect the absorption of study drug.
- •History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.
- •History of allergies or adverse reactions to synthetic BH4 or sepiapterin.
- •Any clinically significant laboratory abnormality as determined by the investigator.
- •Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR <60 milliliters (mL)/minute/1.73 square meter (m^2).
- •Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive GTP cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin-4-alphacarbinolamine dehydratase genes.
研究组 & 干预措施
PTC923
Participants will receive PTC923 7.5 mg/kg (participants 0 to <6 months of age), 15 mg/kg (participants 6 to <12 months of age), 30 mg/kg (participants 12 months to <2 years of age), or 60 mg/kg (participants ≥2 years of age) orally once daily for a minimum of 12 months or until participant experiences lack of efficacy, adverse events (AEs) that lead to discontinuation, withdraws from treatment, or PTC923 is authorized and commercially available in the specific country.
干预措施: PTC923 (Drug)
结局指标
主要结局
Number of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline up to end of study (up to 4 years)
A TEAE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease in a study participant who is administered study drug in this study
Change From Baseline in Dietary Phe/Protein Consumption at Week 26, Measured During Phe Tolerance Assessment Period
时间窗: Baseline, Week 26
Phe tolerance is defined as the total amount of dietary Phe (milligrams \[mg\]/kilogram \[kg\] per day) ingested while maintaining blood Phe levels within the range of 40 to 360 micromoles (μmol)/liter (L) (defined as ≥40 to \<360 μmol/L).
次要结局
- Change From Baseline in Quality of Life (QOL) Using Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire at Months 8, 14, 20, 26, 32, and 38(Baseline, Months 8, 14, 20, 26, 32, and 38)
- Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38(Baseline, Months 8, 14, 20, 26, 32, and 38)
- Palatability of PTC923(Month 1 Day 1)
- Acceptability/Ease of Administration of PTC923(Month 1 Day 1)
- Taste/Flavor Assessment Using a Facial Hedonic Scale(Month 1 Day 1)
- Plasma Sepiapterin Concentration(Month 1 Day 1 up to Month 11 Day 1)
- Plasma BH4 Concentration(Month 1 Day 1 up to Month 11 Day 1)